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Issue 12, 2012
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Targeting the leukocyte activation cascade: Getting to the site of inflammation using microfabricated assays

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Abstract

This paper describes the use of microfabricated devices to study the leukocyte activation cascade (LAC). The devices consist of microchannels fabricated in polydimethylsiloxane using soft lithography. Microfluidics, used to generate physiologically relevant levels of shear flow, was achieved by the simple attachment of a syringe pump. Microchannel surfaces were modified by self-assembled monolayer (SAM) chemistries. The devices were adapted to standard 96-well tissue culture format with microchannels that could accommodate either a monolayer of endothelial cells or a SAM with immobilized chemokines. Chemotaxis was performed using linear gradients of chemokine set in a 3D matrix. Using this approach, we demonstrated robust chemotaxis of primary human leukocytes (PHLs) in response to a gradient of the chemokine CCL2. Rolling and adhesion assays performed under shear flow demonstrated that leukocyte recruitment to the substrate was highly sensitive to both biological and physical forces. CCL2 and CXCL12 treatment of PHLs dose dependently increased activation and adhesion. These actions could be inhibited by the use of peptide or small molecule antagonists. These devices provide a robust platform to perform LAC assays under in vivo-like conditions.

Graphical abstract: Targeting the leukocyte activation cascade: Getting to the site of inflammation using microfabricated assays

  • This article is part of the themed collection: Focus on USA
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Article information


Submitted
07 Nov 2011
Accepted
06 Mar 2012
First published
08 Mar 2012

Lab Chip, 2012,12, 2255-2264
Article type
Paper

Targeting the leukocyte activation cascade: Getting to the site of inflammation using microfabricated assays

E. Kim, O. Schueller and P. M. Sweetnam, Lab Chip, 2012, 12, 2255
DOI: 10.1039/C2LC21078A

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